A. W. Sielenkämper

Arginine vasopressin compromises gut mucosal microcirculation in septic rats

ObjectiveArginine vasopressin (AVP) is increasingly used in the therapy of septic patients with hypotension. However, its effects on the microvascular networks have not been studied in detail. This study was designed to determine the effects of AVP infusion on the villus microcirculation of the septic rat ileum. DesignProspective, placebo-controlled, randomized, single-blinded trial. SettingUniversity research laboratory. SubjectsFifteen male Sprague-Dawley rats. InterventionsTwenty-four hours after cecal ligation and perforation to create sepsis (M1), rats (n = 8) received a continuous AVP infusion to increase mean arterial pressure by 20 mm Hg (M2) and 40 mm Hg (M3) from M1. In the control group (n = 7), an equivalent volume of normal saline was infused. Measurements and Main ResultsVideomicroscopy was performed on 6–10 villi of ileum mucosa at M1 and was repeated at M2 and M3. Blood was drawn to determine plasma levels of AVP and interleukin-6. At M1, both study groups were hypotensive compared with preseptic data (mean arterial pressure, −25%). The increase in mean arterial pressure was linked to supraphysiologic AVP plasma levels and was accompanied by a decrease in mean mucosal blood flow by 76% at M2 and 81% at M3 (p < .001 vs. control). Red blood cell velocity fell by 45% and 47%, respectively (p < .05 vs. control). Whereas periods of arrested villus blood flow increased from 8.1 ± 2.6 secs/min to 43.8 ± 5.2 and 47 ± 6.2 secs/min at M2 and M3 (p < .001), the diameter of terminal arterioles remained unchanged. In addition, AVP infusion further augmented the sepsis-associated increase in interleukin-6 levels (AVP, 905 ± 160 vs. control, 638 ± 55 pg/mL; p = .022). ConclusionsThis study provides evidence for severe abnormalities in gut mucosal blood flow after AVP infusion in septic rats, accompanied by an augmented inflammatory response to the septic injury. The effects of AVP on microvascular blood flow in this model may be related to AVP activities on larger arterioles (>40 &mgr;m), a concomitant reduction in cardiac output, or even both.

Thoracic Epidural Anesthesia Increases Mucosal Perfusion in Ileum of Rats

BACKGROUND Previous studies reported that thoracic epidural anesthesia (TEA) protected against a decrease in gastric intramucosal pH, suggesting that TEA increased gut mucosal perfusion. The current study examines the effects of TEA on ileal mucosa using intravital microscopy in anesthetized rats. METHODS Nineteen rats were equipped with epidural catheters, with the tip placed at T7 through T9. Rats were anesthetized and mechanically ventilated. After midline abdominal incision, the ileum was prepared for intravital microscopy. Videomicroscopy on the ileal mucosa was performed before and after epidural infusion of 20 microliter of bupivacaine 0.4% (TEA group, n = 11 rats) or normal saline (control group, n = 8 rats). Microvascular blood flow in ileum mucosa was assessed offline using computerized image analysis. RESULTS Control rats exhibited unchanged mean arterial pressure and microvascular perfusion. During TEA, mean arterial pressure was decreased compared with the control group (93 +/- 10 vs. 105 +/- 9 mmHg; P < 0.05). Epidural bupivacaine increased red cell velocity in terminal arterioles from 888 +/- 202 to 1,215 +/- 268 micrometer/s (control, 793 +/- 250 to 741 +/- 195 micrometer/s; P < 0.001 between groups). Because arteriolar diameter was not affected, this increase in red cell velocity may represent an increase in arteriolar blood flow. Total intercapillary area (inversely related to perfused capillary density) was unchanged, but for the TEA group the difference between total intercapillary area and the intercapillary area calculated for continuously perfused capillaries was decreased compared with the control group (16 +/- 12 vs. 40 +/- 19%; P < 0.001), indicating a decrease in intermittent (stop-and-go) blood flow in the villus microcirculation. CONCLUSION Thoracic epidural anesthesia increased gut mucosal blood flow and reduced intermittent flow in the villus microcirculation in the presence of a decreased perfusion pressure.

The role of thoracic epidural analgesia in receptor-dependent and receptor-independent pulmonary vasoconstriction in experimental pancreatitis.

BACKGROUND:Acute pancreatitis commonly results in lung injury and deterioration of pulmonary endothelial function and vasoregulation. Despite a variety of potential risks with the use of thoracic epidural analgesia (TEA) in the critically ill, this technique is an important component of pain management in pancreatitis in selected cases. Although there is evidence that epidural analgesia improves lung function through effective pain relief, the influence of continuously applied epidural local anesthetics on pulmonary endothelial dysfunction is still unknown. METHODS:In an in vivo model of TEA in awake rats with acute pancreatitis, we evaluated blood gas analysis, arterial blood pressure, and exhaled nitric oxide. This was followed by in vitro studies of receptor-dependent and receptor-independent pulmonary vasoconstriction using an isolated perfused lung model. Pulmonary myeloperoxidase activity, indicating leukocyte sequestration into the lungs and wet/dry ratio evaluating pulmonary edema, were also measured. RESULTS:Deteriorated oxygenation, metabolic and lactate acidosis, as well as exhaled nitric oxide levels occurring during acute pancreatitis, were reduced by TEA to levels observed in sham-operated animals. TEA also partially ameliorated the hypotension occurring in pancreatitis. In isolated perfused lungs, receptor-dependent vasoconstriction due to angiotensin II was reduced during acute pancreatitis, indicating pulmonary vascular smooth muscle cell dysfunction. Hypoxic pulmonary vasoconstriction was likewise abolished. Treatment with TEA partly restored the vasoreactivity to angiotensin II and hypoxia. Bradykinin-induced vasoconstriction, indicating pulmonary endothelial dysfunction, myeloperoxidase activity and the degree of pulmonary edema, was not influenced by TEA. CONCLUSIONS:Our study demonstrated that TEA improves pancreatitis-associated impairment of pulmonary vasoreactivity and gas exchange.

Einsatz von Vasopressin und Terlipressin bei Sepsis und systemischen Entzündungsreaktionen

ZusammenfassungVasopressin und Terlipressin werden zunehmend als alternative non-adrenerge Vasopressoren in der Kreislauftherapie bei septischen Patienten mit arterieller Hypotonie eingesetzt. Neben ihrem hervorragenden vasopressorischen Effekt vermögen Vasopressin-Analoga jedoch die Makrohämodynamik, das Sauerstoffangebot und den mikrovaskulären Blutfluss negativ zu beeinflussen. Durch diese Effekte können Vasopressin und Terlipressin die Organfunktion möglicherweise kompromittieren und potenziell zur Entwicklung eines Multiorganversagens beitragen. Im Folgenden werden tierexperimentelle und klinische Studien diskutiert, die eine Aussage zur Wirkung von Vasopressin und Terlipressin auf Mikrozirkulation, Sauerstofftransport, Metabolismus und Organfunktion bei Patienten mit Sepsis und systemischen Entzündungsreaktionen („systemic inflammatory response syndrome“, SIRS) erlauben. Obwohl Vasopressin-Analoga vielversprechende Alternativen zur Therapie der katecholaminrefraktären arteriellen Hypotension darstellen, kann bislang keine eindeutige Empfehlung zur Verwendung in dieser Indikation ausgesprochen werden, da es keine prospektive Studie gibt, in der durch den Einsatz von Vasopressin-Rezeptoragonisten ein verbessertes Outcome erzielt wurde.AbstractVasopressin and terlipressin are increasingly used as alternative non-adrenergic vasopressors for hemodynamic support of septic patients with arterial hypotension. Despite excellent vasopressive effects, vasopressin analogues may potentially impair macrohemodynamics, oxygen transport and microvascular blood flow. Due to those unwanted side-effects, vasopressin and terlipressin may potentially compromise organ function and possibly foster the development of multiple organ failure. This review article discusses the results of clinical and experimental studies to judge the effects of vasopressin and terlipressin on microcirculation, oxygen supply, metabolism and organ function in patients with sepsis or systemic inflammatory response syndrome (SIRS). Although vasopressin analogues are emerging as promising alternatives to treat catecholamine-refractory hypotension, there is no evidence that vasopressin receptor agonists improve outcome. To date, vasopressin and terlipressin can, therefore, not be recommended for routine clinical use.

Epidural anesthesia and splanchnic perfusion

To the Editor: Piper et al. reported that during and after aortic surgery, gastric intramucosal pH (pHi) showed a similar decrease from baseline in patients with and without epidural anesthesia. CO2-gap was also comparable between groups.1 These findings are in disagreement with the majority of studies on the effects of epidural anesthesia on splanchnic perfusion during abdominal surgery. Most studies reported beneficial effects of epidural anesthesia, resulting in increased regional blood flow or gastric pHi.1 – 3 Experimental work using intravital microscopy also demonstrated that thoracic epidural anesthesia increases gut mucosal blood flow.4 Others reported that during lumbar epidural blockade, intestinal vasoconstriction resulted due to a compensatory increase in splanchnic sympathetic activity.5 Therefore, beneficial changes in gastrointestinal mucosal blood flow (and pHi, or CO2 gap) cannot be expected if the epidural results in anesthesia outside the area of interest. Usually, investigators who demonstrated evidence for improved splanchnic blood flow during epidural anesthesia performed measurements inside the anesthetized region.2–4 In the study by Piper et al., epidural catheters were inserted at L3–4.1 Therefore, the anesthetic block did not include those sympathetic nerves that supply the gastric wall. The site of pHi measurement and the location of epidural anesthesia were different, thus explaining why epidural anesthesia failed to produce beneficial effects on gastric intramucosal pHi, or CO2 gap. Obviously, the authors missed this important point. With all their patients having received lumbar epidural anesthesia only, the conclusion that epidural bupivacaine has no effect on splanchnic microvascular hemodynamics and pHi was inappropriate.

Thoracoscopic interruption of patent ductus arteriosus compromises cardiopulmonary function in newborn pigs.

Interruption of patent ductus arteriosus (PDA) using video-assisted thoracoscopic surgery (VATS) has recently been introduced into clinical practice. To study cardiovascular and pulmonary function during VATS, we treated 16 newborn pigs (weight 1421 +/- 44 g) with PDA with conventional surgical interruption (CSI; n = 7) or interruption via VATS (n = 9). Measurements of hemodynamics and gas exchange were performed before, during, and after surgery. Systemic perfusion was calculated using Ficks equation. Stress hormones (ACTH, epinephrine, and norepinephrine) were determined before and after surgery. The duration of the surgical procedure was 41 +/- 8 min for CSI and 49 +/- 9 min for VATS (mean +/- SEM). With VATS, PaO2 decreased during and after surgery (P < 0.05), whereas alveolar-arterial PO2 difference (PA-aO2) and PaCO2 were increased (P < 0.05). Compared with CSI after surgery, PaO2 with VATS was decreased (130 +/- 10 vs 171 +/- 12 mm Hg; P < 0.05). Systemic perfusion was lower during VATS (76.7% of baseline) than during CSI (107% of baseline; P < 0.05). Heart rate, mean arterial pressure, and right ventricular end-diastolic pressure remained unchanged with both treatments. Stress hormones were comparable between groups. We conclude that systemic perfusion and oxygenation were impaired during VATS compared with CSI. Therefore, VATS may be contraindicated in pediatric patients with minor cardiopulmonary reserve. Implications: We studied the cardiopulmonary effects of endoscopic interruption of the patent ductus arteriosus in an animal model of newborn pigs. Gas exchange and systemic perfusion were impaired compared with conventional interruption of the patent ductus arteriosus after thoracotomy. (Anesth Analg 1998;87:1037-40)

Einsatz von Vasopressin und Terlipressin bei Sepsis und systemischen Entzündungsreaktionen@@@Vasopressin and terlipressin in sepsis and systemic inflammatory response syndrome: Auswirkungen auf Mikrozirkulation, Sauerstofftransport, Metabolismus und Organfunktion@@@Effects on microcirculation, oxygen transport, metabolism and organ function

ZusammenfassungVasopressin und Terlipressin werden zunehmend als alternative non-adrenerge Vasopressoren in der Kreislauftherapie bei septischen Patienten mit arterieller Hypotonie eingesetzt. Neben ihrem hervorragenden vasopressorischen Effekt vermögen Vasopressin-Analoga jedoch die Makrohämodynamik, das Sauerstoffangebot und den mikrovaskulären Blutfluss negativ zu beeinflussen. Durch diese Effekte können Vasopressin und Terlipressin die Organfunktion möglicherweise kompromittieren und potenziell zur Entwicklung eines Multiorganversagens beitragen. Im Folgenden werden tierexperimentelle und klinische Studien diskutiert, die eine Aussage zur Wirkung von Vasopressin und Terlipressin auf Mikrozirkulation, Sauerstofftransport, Metabolismus und Organfunktion bei Patienten mit Sepsis und systemischen Entzündungsreaktionen („systemic inflammatory response syndrome“, SIRS) erlauben. Obwohl Vasopressin-Analoga vielversprechende Alternativen zur Therapie der katecholaminrefraktären arteriellen Hypotension darstellen, kann bislang keine eindeutige Empfehlung zur Verwendung in dieser Indikation ausgesprochen werden, da es keine prospektive Studie gibt, in der durch den Einsatz von Vasopressin-Rezeptoragonisten ein verbessertes Outcome erzielt wurde.AbstractVasopressin and terlipressin are increasingly used as alternative non-adrenergic vasopressors for hemodynamic support of septic patients with arterial hypotension. Despite excellent vasopressive effects, vasopressin analogues may potentially impair macrohemodynamics, oxygen transport and microvascular blood flow. Due to those unwanted side-effects, vasopressin and terlipressin may potentially compromise organ function and possibly foster the development of multiple organ failure. This review article discusses the results of clinical and experimental studies to judge the effects of vasopressin and terlipressin on microcirculation, oxygen supply, metabolism and organ function in patients with sepsis or systemic inflammatory response syndrome (SIRS). Although vasopressin analogues are emerging as promising alternatives to treat catecholamine-refractory hypotension, there is no evidence that vasopressin receptor agonists improve outcome. To date, vasopressin and terlipressin can, therefore, not be recommended for routine clinical use.